This research project is designed to investigate interactions of enveloped RNA viruses with cells of the murine immune system. The principal virus to be studied is the lactic dehydrogenase virus (LDV), first detected as a passenger virus in tumor-bearing mice and subsequently isolated as a unique infectious agent that is non-cytopathic and produces a persistent viremia in the animal. The virus appears to replicate only in macrophages but it has profound effects on the immune system. More detailed information on the properties and replication of LDV will be essential for understanding how this virus affects the immune response. The specific objectives to be pursued are: (1) The development of better methods to assay for the virus. (2) To investigate the steps in viral replication in macrophage cultures. (3) To determine why the host range of LDV is restricted to mouse macrophages and if any viral-specific macromolecules are synthesized in cells that do not replicate LDV. (4) To ascertain if a nuclear function is required for the replication of LDV and to investigate the inhibitory action of actinomycin D on viral replication. (5) To examine the accumulation of defective interfering particles and determine what role they may have in the replication of LDV in mice.